Adipose tissues can be traditionally classified into white adipose tissue (WAT) and brown adipose tissue (BAT). While WAT stores nutrients as lipids, BAT can dissipate lipids to provide heat in a process called thermogenesis. BAT thermogenesis is dependent on the activation of uncoupling protein-1 (UCP1), which is located in the inner mitochondrial membrane of BAT. When activated, UCP1 uncouples oxidative phosphorylation in mitochondria to dissipate the electrochemical gradient as heat.
In addition to the “classical” and “developmentally programmed” brown adipocytes clustered in defined anatomical BAT depots, a “browning” process, which consists of the induced appearance of UCP1-expressing and multilocular brown adipocytes in WAT depots, often in response to specific stimuli such as prolonged cold exposure and chronic treatment with β3-adrenergic stimuli. These inducible brown adipocytes within classical WAT depots have been called “brite” (brown-in-white) or “beige” adipocytes. The important roles of brite/beige cells in thermoregulation and energy homeostasis are highlighted recently. In adult humans, the predominant form of brown adipocytes is brite/beige cells, which can be induced from WAT under proper stimulation. In light of the promising metabolic benefits of brown adipocytes, intense research has been conducted in recent years to search for physiological, pharmacological and dietary agents that can enhance browning of WAT by induction of UCP1 expression or/and mitochondrial oxidative metabolism. So far, dozens of “browning” agents have been reported, including the sympathetic activators (such as the β3-adrenergic agonists BRL26830A and CL-316243), prostaglandins, PPARα and PPARγ agonists, retinoids, activators of AMP-activated protein kinase, thyroid hormone, bone morphogenetic protein 7 (BMP7), irisin and fibroblast growth factor (FGF)21. While most of these agents exert dual effects on both activation of classical BAT and induction of WAT browning, and some of them (such as prostaglandin, irisin and FGF21) are specific to the browning of WAT. Although some drugs are found to induce browning, they may show strong side effect. Therefore, it is important to look for safer and more effective “browning” food supplements and/or drugs for healthy development and treatment of obesity as well as it associated metabolic disorders.